1. Introduction
Listeria monocytogenes is a Gram-positive, motile facultative anaerobe bacteria that inhibits a broad ecologic niche [
1,
2]. The microorganism can be isolated from soil, water and vegetation, including raw designated also for human consumption without further processing [
3,
4]. Newer chromogenic media may offer advantages in the detection of contaminated food [
5,
6]. The surface contamination of meat and vegetables is common, with up to 15% of these foods harboring the microorganism. Furthermore,
L. monocytogenes is a transient inhabitant of both animal and human gastrointestinal tracts; intermittent carriage suggests possible frequent exposure [
7,
8]. Usually, gut is the source for the microorganisms in case of invasive listeriosis; the virulence factor ActA is associated with carriage development [
9]. The microorganism has a competitive advantage against other Gram-positive and Gram-negative bacteria in cold environments, such as refrigerators; it is also amplified in spoiled food products, possible leading to increased alkalinity. Feeding of spoiled silage with a high pH resulted in epidemics of listeriosis in sheep and cattle [
10]. Several foodborne outbreaks of listeriosis derived from animal epidemics; the first one occurred in Canada and was associated with the ingestion of contaminated coleslaw [
11]. Subsequently, many other foodstuffs have been implicated in different outbreaks, including unpasteurized and pasteurized cheeses and milk or milk derivates [
12,
13,
14,
15,
16,
17,
18,
19,
20,
21,
22,
23], meat products [
24,
25,
26,
27,
28,
29] and fruits and vegetables [
30,
31,
32,
33,
34]. In addition, also hospitalized individuals seem at risk of acquiring
L. monocytogenes infections [
35]. To optimize the tracking of listeriosis cases, the whole-genome sequencing has been developed and then replaced older techniques as serotyping [
36,
37]. However, it remains not completely understood why outbreaks of listeriosis can occur in humans; a possible enhancement of organism-specific virulence factors may play a role in developing epidemic dissemination. Nevertheless, all isolates of
L. monocytogenes are able to produce all the virulence factors characteristic of the species.
Also sporadic cases of listeriosis can be foodborne related; reports of sporadic cases of
L. monocytogenes infection in absence of documented outbreaks have been associated with different food products that could represent vehicles for the occurrence of sporadic invasive listeriosis in humans [
38]. Consequently,
L. monocytogenes can be considered a common contaminant of food products and the ingestion of small quantitative of this microorganism occurs frequently in humans [
39].
L. monocytogenes usually grows in biofilms or in food products not undergoing to pasteurization and kept at cold temperature. Invasive diseases occur when the ingestion of a large number of microorganisms overwhelm the innate host-defense systems at gastrointestinal, liver or spleen level. Although the annual rate of sporadic listeriosis in Europe and North America is usually < 1/100000 population per year [
40,
41,
42], the development of this infection is associated with a high burden of costs [
43,
44]. Sporadic listeriosis usually follows seasonal variations, being more common during spring- and summertime, mainly associated to the increased consumption of higher-risk products during the warmer period. In addition, the risk of developing invasive listeriosis could be associated with the presence of pre-existing damages on the gastrointestinal mucosa due to other microorganisms that usually induced viral gastroenteritis and that have seasonal patterns that may overlap with those of listeriosis. These damages may allow translocation of
L. monocytogenes from the gastrointestinal tract with subsequent development of invasive diseases [
45].
Host-specific conditions also contributed to increase the risk of invasive listeriosis [
46,
47]. In particular, cases of invasive listeriosis are most commonly described in the first month of life or in elderly individuals. The fetus is mainly infected during maternal sepsis or secondary to peri-vaginal or peri-anal colonization of the mother, with transmission occurs through the birth canal. Infants usually don’t have adequate host defense, mainly in cases of impairment of macrophage and cell-mediated immune function; therefore, invasive listeriosis can easily develop in case of colonization of the liver, respiratory tract or gastrointestinal tract. Pregnant women have usually a decreased gastrointestinal motility and also a slight impairment of cell-mediated immune response to
L. monocytogenes; both these conditions may predispose to invasive listeriosis with transplacental infection of the infant [
48,
49,
50,
51] that can finally lead to a delivery of a premature and often severely ill newborn. Spontaneous recovery of the mother from invasive listeriosis normally occurs after the delivery; the administration of specific and appropriate antibiotic therapy can improve the prognosis of the infant and also accelerate the clinical recovery of the mother. When the infant is infected through a colonized birth canal, clinical disease in the infant usually develop 7 to 14 days later. A direct cutaneous invasion is unlikely in this context; aspiration of
L. monocytogenes into the respiratory tract or by swallowing of the microorganism can occur only during the incubation period. At the moment, a unique outbreak of neonatal listeriosis has been described.
L. monocytogenes was spread through contaminated mineral oil used to clean infants after delivery from healthy mothers, with cross contaminations of shared mineral oil; the index case was infected through the placental route of maternal-fetal infection [
52].
The increased risk of invasive listeriosis in elderly usually reflects the increasing incidence of other immunosuppressive conditions in this specific population, such as solid or hematological malignancies, chronic diseases leading to immunological impairment such as diabetes or renal failure, or immunosuppressive treatments. In particular, malignancies may lead to abnormalities of gastrointestinal mucosa and impairment of effective macrophage function in liver, spleen and peritoneum, both directly or secondary to chemotherapy or radiation-induced damages, finally favoring bacterial translocation from the gastrointestinal tract. The increasing use of immunosuppressive treatments with a specific effect on cell-mediated immune function as corticosteroids or cyclosporine A, as well as the use of biologic treatments with immune modulator effect as tumor necrosis factor-alpha inhibitors can also contribute to an augmented risk of invasive listeriosis [
53,
54,
55].
Among the cause of immunosuppression, HIV infection has been linked to the occurrence sporadic invasive listeriosis [
56]. In particular, earlier studies described a 500-1000-fold greater risk of developing invasive listeriosis in HIV-infected individuals compared to general population. Subsequently, a progressive reduction of reported cases has been observed, due to dietary recommendations to prevent foodborne illnesses and, above all, due to the wide use of trimethoprim-sulfamethoxazole as
Pneumocystis jirovecii pneumonia prophylaxis to which
L. monocytogenes is also susceptible; furthermore, a possible contribute to the reduction of cases may be secondary to the widespread use of more efficacy antiretroviral treatments that induce a restoration of immune system function [
57].
L. monocytogenes is overall considered one of the most important foodborne pathogen associated with the occurrence of febrile gastroenteritis outbreaks. Several foods have been described as vehicles of these outbreaks, including fresh cheese, ready-to-eat meat, shrimps, rice or corn salad and chocolate milk [
15,
22,
58,
59,
60,
61,
62,
63]. In these outbreaks, symptoms developed soon after ingestion (approximately 24 hours) and attack rates were significantly greater when compared to invasive listeriosis. These high attack rates are not usually related to enhanced intrinsic virulence of the
L. monocytogenes strain but to a heavily contamination of the ingested food.
A reduction in the overall incidence of listeriosis could be due to a larger promotion of dietary recommendations to high-risk individuals, including pregnant women, patients with malignancies or underwent to transplantation [
64]. More probably, this reduction could be due to the worldwide promotion of awareness in the food-processing industry, including hazard analysis at critical control point (HACCP) [
65,
66] and, above all, to programs to reduce food contamination with different microorganisms including
L. monocytogenes,
Salmonella spp.,
Escherichia coli and
Campylobacter spp [
67,
68,
69]. These activities provided an augmented protection for fresh, unprocessed food products that may not have been cooked or pasteurized and that are at higher risk of convey foodborne illnesses. In addition to hazard analysis, regulatory agencies significantly implemented the control of microorganisms with potential ability to contaminate food. The U.S. Food and Drug Administration developed strict recommendations for the control of
L. monocytogenes in the food industry [
70], mainly including the use of whole-genomic sequences (WGS) [
71]. Recently, Conrad et al. [
72] described how, starting from 5 cases of invasive listeriosis in Kansas, the use of WGS permitted to identify
L. monocytogenes contamination of ice-cream products in three other states; the Company facilities where the ice-creams were produced were located in Texas and Oklahoma, suggesting long-standing contamination. Other countries have adopted less stringent guidelines, allowing a small amount of contamination (<10
2CFU/g) to balance the protection of public health and the needless condemnation of otherwise edible food products. While invasive listeriosis seems more common in some European countries than in United States, it is still unclear whether these differences can be attributed to the less stringent standards in Europe. It remains therefore debatable if a “zero tolerance” approach for
L. monocytogenes contamination of food could be preferable to a risk assessment approach [
73].